POS0006 IDENTIFICATION OF FIBROTIC AND FIBROLYTIC ENDOTYPES IN RHEUMATIC DISEASE COHORTS
Authors: A. C. Bay-Jensen, S. Holm Nielsen, P. Frederiksen, M. Karsdal, W. Chen, S. Gao
Journal: Annals of the Rheumatic Diseases (2022)

Background Ankylosing spondylitis (AS), psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE) are distinct diseases with common molecular features, such as an imbalance in fibrolysis and fibrosis of connective and calcified tissues. Type III, IV and VI collagens are abundant in connective tissue, and type I, II and X of the skeletal tissue. Blood biomarkers are available to measure fibrolysis (C1M, C2M, C3M, C4M, C6M, C10C) and fibrosis (PRO-C1, PRO-C2, PRO-C3, PRO-C4, PRO-C6) of these collagens. Objectives To profile AS, PsA and SLE patients (pts) using blood biomarkers of collagen formation and degradation. Methods Baseline serum samples from consenting pts of the AS ( NCT02437162 /NCT02438787), PsA (NCT0315828), and SLE ( NCT02349061 ) studies were included in the analyses. Healthy donor samples were acquired from Discovery LS. Biomarkers were measured by immunoassays. Biomarker levels were compared by Kruskal-Wallis test. Before hierarchical clustering (Ward.D2), biomarker levels were log-transformed and standardized by median centering and scaling by median absolute deviation (MAD). Results When compared with healthy individuals, VICM was elevated in all indications (although markedly less so in SLE pts). The fibrosis marker PRO-C3 was elevated in all indications vs. healthy, while PRO-C4 and PRO-C6 were elevated only in AS and PsA. The fibrolysis markers C3M, C4M and C6M were elevated in all indications. The cartilage fibrosis marker PRO-C2, but not C2M, was elevated in AS and PsA, but not in SLE, ps. The bone fibrosis marker PRO-C1 was at the level of healthy for all. The fibrolysis marker C1M was elevated in all, while elevated C10C was seen only in PsA and SLE, pts (Table 1). Four clusters (C) of blood markers were extracted (Figure 1). C1 was characterized by low biomarker levels (68% of healthy, 1% of PsA, 3% of SLE pts). C2 was described by high levels of C10C and median levels of VICM (20% of healthy, 12% of AS, 19% of PsA, 42% of SLE pts). C3 was described by median biomarker levels (8% of healthy, 67% of AS, 48% of PsA, 46% of SLE pts). C4 had high biomarker levels (4% of healthy, 21% of AS, 31% of PsA, 9% of SLE pts). Conclusion Fibrosis and fibrolysis blood biomarkers were significantly elevated in AS, PsA and SLE pts. Subsets of pts from each indication were found in clusters with either low (C1/2), median (C3) or high (C4) levels of fibrosis/fibrolysis biomarkers. These findings may provide a first step towards precision medicine for guiding the use of anti-inflammatory vs. anti-fibrotic treatments in pts with rheumatological disorders. Disclosure of Interests Anne-Christine Bay-Jensen Shareholder of: Nordic Bioscience A/S, Employee of: Nordic Bioscience A/S, Signe Holm Nielsen Shareholder of: Nordic Bioscience A/S, Employee of: Nordic Bioscience A/S, Peder Frederiksen Employee of: Nordic Bioscience A/S, Morten Karsdal Shareholder of: Nordic Bioscience A/S, Employee of: Nordic Bioscience A/S, Warner Chen Employee of: Janssen Research &amp; Development, Sheng Gao Employee of: Janssen Research &amp; Development